Retatrutide LY-3437943 benefits in weight loss 17.5% in 24weeks

Retatrutide is arguably the latest promising drug for weight loss and the treatment of type 2 diabetes in obese/overweight patients. It has a completely new mode of action, and clinical trials have shown that it is more effective in weight loss. 

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Some approved weight loss products were originally developed to treat type 2 diabetes and work based on things like appetite control and delayed gastric empting. Retatrutide, a new drug in development for the treatment of obesity, is a triple receptor agonist that activates the GLP-1(glucagon-like peptide-1) receptor,GIP(Glucose-dependent insulin stimulating) receptor and GCGR (glucagon) receptors in the body, an unprecedented way to lose weight.

How does Retatrutide lose weight?

A preliminary understanding of how Retatrutide works for weight loss can be found in the three receptors it acts on.

GLP-1: Glucagon-like peptide 1

GLP-1 is the key word in the treatment of type 2 diabetes, which mainly plays a role in regulating blood sugar in the body. it inhibits appetite and slows stomach emptying, helping to lower blood sugar while also helping with weight loss, which is why drugs used to treat type 2 diabetes can also be used for weight loss.

GIP: Glucose-dependent insulin-promoting polypeptide

GIP, also known as gastric inhibitory peptides, reduces hunger and increases satiety by reducing the secretion of stomach acid and the speed at which food is transported through the stomach.

Compared with single GLP-1 agonists, GLP-1 and GIP dual agonists increase overall energy expenditure and reduce caloric intake, thus achieving better weight loss. This is the mode of action of Tirzepatide, a new type 2 diabetes drug developed by Eli Lilly and Co., which is a double receptor agonist for GLP-1 and GIP, and is a completely new attempt. Its effectiveness has been proven and it has been approved by the FDA. Tirzepatide’s weight loss was equally impressive, showing an average weight loss of 22.5 percent (about 52 pounds) after 72 weeks of use, while Semaglutide experienced an average weight loss of about 15 percent (34 pounds) after 68 weeks.

Retatrutide is another Lilly innovation that has a completely new mode of action, activating GCG(glucagon) receptors in addition to GLP-1 receptors and GIP receptors.

What is GCG(Glucagon)?

GCG ,is glucagon, acts as the opposite of insulin, which reduces glucose levels outside the cell. So how does Retatrutide’s activation of glucagon receptors play a role in weight loss?

Glucagon promotes glycogen breakdown, converting stored glycogen into glucose, which is then released into the bloodstream to provide energy for the body. This pattern increases blood sugar to a certain extent, but it also promotes lipolysis and enhances the oxidation of fatty acids, converting them into usable energy for the body. Glucagon also reduces the synthesis of fatty acids in fat tissue and liver, and promotes lipolysis in these tissues, providing an energy source for tissues such as skeletal muscle.

Therefore, compared with the hypoglycemic effects of GLP-1 and GIP, glucagon is more conducive to reducing fat, breaking down fat, and promoting metabolism. Retatrutide acts as a GLP-1,GIP, and glucagon triple receptor agonist with better weight loss results. Clinical trials showed that obese, overweight patients experienced an average weight loss of 24.2 percent (about 57.8 pounds or 26.2kg) after 48 weeks of use of Retatrutide. This is another milestone for any weight-loss drug, so even though Retatrutide has just completed Phase II clinical trials, it is already attracting a lot of attention.

Retatrutide weight loss trial and treatment of type 2 diabetes trial

Both semaglutide and Tirzepatide are have excellent weight loss results, however, they developing by testing their efficacy in the treatment of type 2 diabetes, receiving FDA approval for the treatment of type 2 diabetes, then verifying their weight loss effects, and then receiving ( waiting for ) FDA approval for weight loss.

Retatrutide has moved its weight loss validation forward, conducting both a weight loss trial and a type 2 diabetes trial that looks promising.

Retatrutide weight loss

In the Retatrutide weight loss trial, patients must have a BMI of 30 kg/m2 or more, or a BMI of 27 kg/m2 and have at least one weight-related disease. There are total of 338 adults in the trial. Participants received doses of Retatrutide 1mg, 4mg, 8mg, 12mg and placebo.

Respectively, after 24 weeks of treatment with Retatrutide 1mg, 4mg, 8mg, 12mg ,participants lost 7.2%, 12.9%, 17.3%, 17.5%.The placebo group lost 1.6 %.

After 48 weeks of treatment, Retatrutide doses of 1mg, 4mg, 8mg, and 12mg, participants lost 8.7%, 17.1%, 22.8%, and 24.2%, respectively, compared with 2.1% in the placebo group.

From this, we can see that R has a very significant weight loss effect in the population with a BMI exceeding 30, and the effect is better with increasing dosage. But this does not mean that we can increase the dosage arbitrarily in pursuit of better weight loss effects.                  

Retatrutide treats type 2 diabetes

The double receptor agonist Tirzepatide has been approved by the FDA for the treatment of type 2 diabetes, and the triple receptor agonist Retatrutide for the treatment of diabetes will not be discussed here, but we will mainly look at the weight loss data in this trial.

Of the 281 people with type 2 diabetes recruited, they had a BMI of 25-50kg/m2, so the lightest (BMI of 25) were relatively leaner than the lightest (BMI of 27) in the weight loss trial. The trial received doses of Retatrutide of 0.5mg, 4mg(initial dose of 2mg), 4mg(initial dose of 4mg), 8mg(initial dose of 2mg), 8mg(initial dose of 4mg), 12mg(initial dose of 2mg) and placebo. After 36 weeks, patients receiving Retatrutide doses of 0.5mg, 4mg(initial dose of 2mg), 4mg(initial dose of 4mg), 8mg(initial dose of 2mg), 8mg(initial dose of 4mg), and 12mg(initial dose of 2mg) lost 3.19%, 7.92%, 7.92%, respectively. 10.37%, 16.81%, 16.34%, 16.94% of patients in the placebo group lost an average of 3% of their body weight.

Summary of the Retatrutide weight loss trial and the Treatment of Type 2 diabetes trial

Both in weight loss trials and in the treatment of type 2 diabetes, the weight loss effect shown by Retatrutide is huge, we can compare the data of Semaglutide and Tirzepatide:

• After 68 weeks of Semaglutide, the average weight loss was about 15%.
• After 72 weeks of Tirzepatide use, the average weight loss was 22.5%.
• After 24 weeks of Retatrutide, the average weight loss was 17.5%.
• After 48 weeks of Retatrutide use, the average weight loss was 24.2%.

From the above data, you can see that Retatrutide loses weight faster and loses more weight.

Comparing weight loss data from the Retatrutide weight loss trial and the Type 2 diabetes trial:

In the Retatrutide weight loss trial, the average weight loss after 24 weeks was 17.5%.

After 36 weeks of Retatrutide in the type 2 diabetes trial, the average weight loss was 16.94%;

From these data, we can know that patients with a smaller weight base and type 2 diabetes lose weight more slowly than obese and overweight patients without type 2 diabetes.

Therefore, for obese, overweight people who do not have type 2 diabetes, Retatrutide has better weight loss results. Moreover, the larger the weight base, the more weight loss using Retatrutide, the faster the weight loss.

In the Retatrutide trial, none of the patients had reached a weight plateau, meaning they would have continued to lose weight if they continued to use Retatrutide.

Retatrutide for weight loss advantages

We can also see the advantage of Retatrutide for weight loss in its mode of action, which has one more receptor of action – glucagon receptor – than Tirzepatide. In clinical studies, scientists have demonstrated the important contribution of glucagon receptors to regulating energy expenditure. We can not explain Weight loss after treatment with Retatrutide  simply by inhibiting food intake; in the trial, Retatrutide increased overall metabolic levels and increased energy expenditure. Compared to people in weight loss who tend to lose lean muscle mass first, weight loss with Retatrutide can retain lean muscle mass and reduce fat synthesis and increase fat breakdown.

This is like the cutting mode of action of anabolic steroids, which inhibits fat production and increases fat breakdown while retaining lean muscle mass. In the process, it produces energy for the skeletal muscles and other parts, improving the user’s exercise level.

Glucagon promotes liver glycogenolysis and gluconeogenesis, reduces fatty acid synthesis in the liver, de-fatten your liver, and helps reduce the long-term harm of obesity on the heart, metabolism, kidneys and liver. In clinical trials of patients treated with Retatrutide, 9 out of 10 patients with nonalcoholic fatty liver disease returned to normal liver fat mass after 48 weeks of treatment.

Retatrutide for weight loss advantages review

A healthy lifestyle requires “keeping your mouth shut and your legs open.” However, the increasing number of obese people proves that too many people cannot do either of these things. Many weight-loss drugs are from the suppression of appetite, slow food digestion, increase satiety, reduce hunger and other aspects of the start, are indirect to help obese patients “control the mouth.” However, drugs do not help patients move their legs. In the process of losing weight, many people often have no extra energy to exercise due to reduced calorie intake and hunger. Retatrutide is an innovative model that burns fat to provide extra energy for the body to exercise while consuming fewer calories, helping obese and overweight patients lose weight more healthily. Thanks to its new mode of action, use Retatrutide to lose weight faster and more.

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